Pre-operative Intra-nasal Dexmedetomidine or Insulin for Prevention of Early Post-operative Cognitive Dysfunction in Patients Undergoing Elective Coronary Artery Bypass Graft.

Pre-operative Intra-nasal Dexmedetomidine or Insulin for Prevention of Early Post-operative Cognitive Dysfunction in Patients Undergoing Elective Coronary Artery Bypass Graft. A Comparative Randomized Bi-centric Study

On pump coronary revascularization is a very common leading cause for post-operative cognitive dysfunction regarding patient age grouping and diffuse systemic inflammatory response induced by bypass machine . Many factors are incriminated as pre-operative sleep disturbance, previous history of neurocognitive dysfunction. The accumulating evidence refers to an incidence between 20-40% with majority among geriatric population. The primary pathology is still elusive and many trials are under evaluation. Neuro-inflammation, hypo perfusion, fat emboli and reperfusion injury are among the most postulative aetiologias. The corner stone in the pathology of postoperative cognitive dysfunction is abnormal sleep rhythm. Intra-nasal insulin can provide neuroprotection via providing insulin growth factor and obtund neuronal apoptosis , while dexmedetomidine can antagonize neural-degeneration via regulation of systematic inflammatory cytokines including interleukin 1β, tumor necrosis factor-α, and NF-κB, inhibiting the expressions of Toll-like receptor , and through α2 adrenoceptor-mediated anti-inflammatory pathways

Study Overview

• Status: Completed
• Conditions: Post Operative Cognitive Dysfunction
• Intervention / Treatment: Drug: intranasal saline group; Drug: intranasal insulin; Drug: Intranasal dexmedetomidine

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Al Fayyum, Egypt
    • Fayoum University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult population, 60 years or above, both sex, candidate for elective on pump coronary revascularization

Exclusion Criteria:

• patient refusal
• combined reperfusion and valve replacement operations.
• Emergency or redo CABG.
• preoperative MMSE score less than 20
• preoperative cardiomyopathy (ejection fraction <40%).
• previous history of cerebrovascular stroke or carotid endarterectomy, dementia, language, hearing or visual impairment precluding accurate neurocognitive assessment.
• history of heparin resistance.
• chronic use of hypnotics (>3 times weekly for >4 weeks), mood stabilizing drugs (lithium, Na valoprate, anticonvulsants) or melatonin.
• pre-operative pacing.
• recent nasal surgery (<3 months), prior maxillofacial trauma with nasal deformity, nasal polyposis or severe allergic rhinitis.
• severe obstructive sleep apnea (apnea hypopnea index >30), central sleep apnea or obesity-hypoventilation syndrome, and planned postoperative non-invasive ventilation.
• Chronic acholic population Alcohol Use Disorders Identification Test (AUDIT) score ≥8 for men or ≥7 for women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group	Drug: intranasal saline group; 3 ml of saline 0.9 % twice daily for 2 days preoperatively at fixed time ( 9 am and 6 pm)
Active Comparator: Dexmedetomidine group	Drug: Intranasal dexmedetomidine; 1.5 mic/kg on 3 ml saline 0.9% at 9 PM at night of surgery and 30 minutes before anesthesia induction
Active Comparator: Insulin group	Drug: intranasal insulin; 20 IU of regular insulin on 3 ml saline 0.9% twice daily for 2 days preoperative via mucosal atomization device at fixed times ( 9 am, 6 pm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini mental state examination	Acute cognitive assessment, score from 0-10 = severe sementia, 10-20 = moderate dementia, 20-25= mild , 25-30= questionably significabt	PREOPERATIVE, 1,3,5, 7 days , on hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU stay	Days from ICU admission postoperative and discharge to word	one week
procedure related complication	bradycardia, spasm, cough,	3 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Richards-Campbell Sleep Questionnaire	sleep quality . The counting method was recorded with numbers (0 points to 100 points). The higher the score, the higher the sleep quality star.	DAILY ( EARLY MORNING at 8-9 AM ) THROUHGOUT ICU stay (10 DAYS)
Confusion assessment method - ICU	POST PERATIVE DELERIUM. CAM (yes or no) includes four aspects: (1) acute onset and fluctuat- ing course, (2) inattention, (3) incoherent thinking, and (4) altered consciousness; the presence of both (1) and (2), and one of (3) or (4) is diagnostic of POD With a total score of 30, a higher score indicates a lower incidence of neurocognitive dysfunction	TWICE DAILY UNTIL ICU DISCHARGE ( 10 DAYS)
transcranial doppler	Pulsatality index ( PI) > 0.8 means severe vasospasm	preoperative, 1 day, 3 days, 5, 7 days
transcranial doppler	resistive index .. 0.8> severe spasm	preoperative, 1 day, 3 days, 5, 7 days
change in MMSE	number and percentage of population with ≥2-point decline in MMSE from preoperative value	1,3,5,7 days from ICU admission and on hospital discharge (3 WEEKS POST OPERATIVE)
Montreal cognitive assessment		preoperative and at ONE WEEK post operative

Collaborators and Investigators

• Sponsor: Minia University

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2024
• Primary Completion (Actual): May 14, 2026
• Study Completion (Actual): May 15, 2026

Study Registration Dates

• First Submitted: December 14, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 23, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Postoperative Complications; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Postoperative Cognitive Complications; Cognitive Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: 640/R

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No